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TRP channel

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https://www.readbyqxmd.com/read/28523109/discovery-of-gsk2193874-an-orally-active-potent-and-selective-blocker-of-transient-receptor-potential-vanilloid-4
#1
Mui Cheung, Weike Bao, David J Behm, Carl A Brooks, Michael J Bury, Sarah E Dowdell, Hilary S Eidam, Ryan M Fox, Krista B Goodman, Dennis A Holt, Dennis Lee, Theresa J Roethke, Robert N Willette, Xiaoping Xu, Guosen Ye, Kevin S Thorneloe
Transient Receptor Potential Vanilloid 4 (TRPV4) is a member of the Transient Receptor Potential (TRP) superfamily of cation channels. TRPV4 is expressed in the vascular endothelium in the lung and regulates the integrity of the alveolar septal barrier. Increased pulmonary vascular pressure evokes TRPV4-dependent pulmonary edema, and therefore, inhibition of TRPV4 represents a novel approach for the treatment of pulmonary edema associated with conditions such as congestive heart failure. Herein we report the discovery of an orally active, potent, and selective TRPV4 blocker, 3-(1,4'-bipiperidin-1'-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide (GSK2193874, 28) after addressing an unexpected off-target cardiovascular liability observed from in vivo studies...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28522036/transient-receptor-potential-trp-channel-function-in-the-reproductive-axis
#2
REVIEW
Viktoria Götz, Sen Qiao, Andreas Beck, Ulrich Boehm
Transient receptor potential (TRP) channels play important functional roles in the signal transduction machinery of hormone-secreting cells and have recently been implicated in reproductive physiology. While expression studies have demonstrated TRP channel expression at all levels of the hypothalamic-pituitary-gonadal (hpg) axis, functional details about TRP channel action at the level of the individual cells controlling reproduction are just beginning to emerge. Canonical TRP (TRPC) channels are prominently expressed in the reproductive center of the neuroendocrine brain, i...
May 3, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28516902/role-of-transient-receptor-potential-channels-in-heart-transplantation-a-potential-novel-therapeutic-target-for-cardiac-allograft-vasculopathy
#3
Shuo Ma, Yue Jiang, Weiting Huang, Xintao Li, Shuzhuang Li
Heart transplantation has evolved as the criterion standard therapy for end-stage heart failure, but its efficacy is limited by the development of cardiac allograft vasculopathy (CAV), a unique and rapidly progressive form of atherosclerosis in heart transplant recipients. Here, we briefly review the key processes in the development of CAV during heart transplantation and highlight the roles of transient receptor potential (TRP) channels in these processes during heart transplantation. Understanding the roles of TRP channels in contributing to the key procedures for the development of CAV during heart transplantation could provide basic scientific knowledge for the development of new preventive and therapeutic approaches to manage patients with CAV after heart transplantation...
May 18, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28516266/constitutive-calcium-entry-and-cancer-updated-views-and-insights
#4
REVIEW
Olivier Mignen, Bruno Constantin, Marie Potier-Cartereau, Aubin Penna, Mathieu Gautier, Maxime Guéguinou, Yves Renaudineau, Kenji F Shoji, Romain Félix, Elsa Bayet, Paul Buscaglia, Marjolaine Debant, Aurélie Chantôme, Christophe Vandier
Tight control of basal cytosolic Ca(2+) concentration is essential for cell survival and to fine-tune Ca(2+)-dependent cell functions. A way to control this basal cytosolic Ca(2+) concentration is to regulate membrane Ca(2+) channels including store-operated Ca(2+) channels and secondary messenger-operated channels linked to G-protein-coupled or tyrosine kinase receptor activation. Orai, with or without its reticular STIM partner and Transient Receptor Potential (TRP) proteins, were considered to be the main Ca(2+) channels involved...
May 17, 2017: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/28508310/trpc-channel-downstream-signaling-cascades
#5
Zhuohao He
The family of TRP channel is comprised of a large group of cation-permeable channels, displaying as signaling integrators for sensing extracellular stimulus and initiating intracellular signaling cascades. This chapter offers a brief review of the signaling molecules related to TRPC channels, the first identified mammalian TRP family. Besides the signaling molecules involved in TRPC activation, I will focus on their upstream and downstream signaling cascades and the molecules involved in their intracellular trafficking...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28508309/trpc-channel-structure-and-properties
#6
Shengjie Feng
TRPC channels are the first identified members in the TRP family. They function as either homo- or heterotetramers regulating intracellular Ca(2+) concentration in response to numerous physiological or pathological stimuli. TRPC channels are nonselective cation channels permeable to Ca(2+). The properties and the functional domains of TRPC channels have been identified by electrophysiological and biochemical methods. However, due to the large size, instability, and flexibility of their complexes, the structures of the members in TRPC family remain unrevealed...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28508308/trp-channel-classification
#7
Hongyu Li
The transient receptor potential (TRP) ion channels are named after the discovery of the photo-transducted channels in Drosophila. TRPs, activated by various extracellular and intracellular stimuli, play a plethora of physiological and pathological roles. There are seven families of TRPs including TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPP (polycystin), TRPML (mucolipin), and TRPN (Drosophila NOMPC) in mammals. In yeast, the eighth TRP family was recently identified and named as TRPY...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28499580/transient-receptor-potential-trp-channels-as-molecular-targets-in-lung-toxicology-and-associated-diseases
#8
REVIEW
Alexander Dietrich, Dirk Steinritz, Thomas Gudermann
The lungs as the gateways of our body to the external environment are essential for gas exchange. They are also exposed to toxicants from two sides, the airways and the vasculature. Apart from naturally produced toxic agents, millions of human made chemicals were produced since the beginning of the industrial revolution whose toxicity still needs to be determined. While the knowledge about toxic substances is increasing only slowly, a paradigm shift regarding the proposed mechanisms of toxicity at the plasma membrane emerged...
April 26, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28475214/the-angiotensin-ii-receptor-type-1b-is-the-primary-sensor-of-intraluminal-pressure-in-cerebral-artery-smooth-muscle-cells
#9
Paulo W Pires, Eun-A Ko, Harry A T Pritchard, Michael Rudokas, Evan Yamasaki, Scott Earley
Myogenic vasoconstriction, which reflects the intrinsic ability of smooth muscle cells to contract in response to increases in intraluminal pressure, is critically important for the autoregulation of blood flow. In SMC from cerebral arteries, increasing intraluminal pressure engages a signalling cascade that stimulates cation influx through transient receptor potential (TRP) melastatin 4 (TRPM4) channels to cause membrane depolarization and vasoconstriction. Substantial evidence indicates that the angiotensin II receptor type 1 (AT1 R) is inherently mechanosensitive and initiates this signalling pathway...
May 5, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28473752/spontaneous-ca-2-influx-in-drosophila-pupal-neurons-is-modulated-by-ip3-receptor-function-and-influences-maturation-of-the-flight-circuit
#10
Sumita Chakraborty, Gaiti Hasan
Inositol 1,4,5-trisphosphate receptors (IP3R) are Ca(2+) channels on the neuronal endoplasmic reticulum (ER) membrane. They are gated by IP3, produced upon external stimulation and activation of G protein-coupled receptors on the plasma membrane (PM). IP3-mediated Ca(2+) release, and the resulting depletion of the ER store, triggers entry of extracellular Ca(2+) by store-operated Ca(2+) entry (SOCE). Mutations in IP3R attenuate SOCE. Compromised IP3R function and SOCE during pupal development of Drosophila leads to flight deficits and mimics suppression of neuronal activity during pupal or adult development...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28462107/role-of-transient-receptor-potential-melastatin-type-7-channel-in-gastric-cancer
#11
REVIEW
Byung Joo Kim, Chansik Hong
Transient receptor potential (TRP) proteins are a family of ion channels, which are responsible for a wide array of cellular functions. In particular, TRP melastatin type (TRPM) 7 is expressed everywhere and permeable to divalent cations such as Mg(2+) and Ca(2+). It contains a channel and a kinase domain. Recent studies indicate that activation of TRPM7 plays an important role in the growth and survival of gastric cancer cells. In this review, we describe and discuss the findings of recent studies that have provided novel insights of the relation between TRPM7 and gastric cancer...
June 2016: Integr Med Res
https://www.readbyqxmd.com/read/28459611/%C3%AE-arrestin-1-bridging-gpcrs-to-active-trp-channels
#12
Zuying Chai, Yang Chen, Changhe Wang
No abstract text is available yet for this article.
May 1, 2017: Channels
https://www.readbyqxmd.com/read/28449103/novel-degenerative-and-developmental-defects-in-a-zebrafish-model-of-mucolipidosis-type-iv
#13
Huiqing Li, Wuhong Pei, Sivia Vergarajauregui, Patricia M Zerfas, Nina Raben, Shawn M Burgess, Rosa Puertollano
Mucolipidosis type IV (MLIV) is a lysosomal storage disease characterized by neurologic and ophthalmologic abnormalities. There is currently no effective treatment. MLIV is caused by mutations in MCOLN1, a lysosomal cation channel from the transient receptor potential (TRP) family. In this study we used genome editing to knockout the two mcoln1 genes present in Dario rerio (zebrafish). Our model successfully reproduced the retinal and neuromuscular defects observed in MLIV patients, indicating that this model is suitable for studying the disease pathogenesis...
April 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28448473/transcriptomic-analysis-of-calcium-remodeling-in-colorectal-cancer
#14
Enrique Pérez-Riesgo, Lucía G Gutiérrez, Daniel Ubierna, Alberto Acedo, Mary P Moyer, Lucía Núñez, Carlos Villalobos
Colorectal cancer (CRC) cells undergo the remodeling of intracellular Ca(2+) homeostasis, which contributes to cancer hallmarks such as enhanced proliferation, invasion and survival. Ca(2+) remodeling includes critical changes in store-operated Ca(2+) entry (SOCE) and Ca(2+) store content. Some changes have been investigated at the molecular level. However, since nearly 100 genes are involved in intracellular Ca(2+) transport, a comprehensive view of Ca(2+) remodeling in CRC is lacking. We have used Next Generation Sequencing (NGS) to investigate differences in expression of 77 selected gene transcripts involved in intracellular Ca(2+) transport in CRC...
April 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28440188/trp-channels-as-novel-targets-for-endogenous-ligands-focus-on-endocannabinoids-and-nociceptive-signalling
#15
Maksim V Storozhuk, Alexander V Zholos
The endocannabinoid system is gaining steadily increasing research interest as its important role in the regulation of many fundamental physiological processes becomes more and more evident. One area which received particularly significant attention concerns targeting the endocannabinoid system as a useful strategy in pain control, especially in refractory, difficult to treat cases of chronic pain. Apart from the classical targets of cannabinoids, the CB1 and CB2 receptors, several members of the large TRP family of Ca2+-permeable cation channels have been designated as "ionotropic cannabinoid receptors" to highlight their role in cannabinoid signalling...
April 24, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28437833/transient-receptor-potential-trp-channels-and-exercise-associated-muscle-cramping-eamc-a-tale-of-multiple-complexities
#16
EDITORIAL
M P Schwellnus, M D Hoffman
No abstract text is available yet for this article.
April 24, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28432033/lipids-as-central-modulators-of-sensory-trp-channels
#17
REVIEW
Maria Grazia Ciardo, Antonio Ferrer-Montiel
The transient receptor potential (TRP) ion channel family is involved in a diversity of physiological processes including sensory and homeostatic functions, as well as muscle contraction and vasomotor control. Their dysfunction contributes to the etiology of several diseases, being validated as therapeutic targets. These ion channels may be activated by physical or chemical stimuli and their function is highly influenced by signaling molecules activated by extracellular signals. Notably, as integral membrane proteins, lipid molecules also modulate their membrane location and function either by direct interaction with the channel structure or by modulating the physico-chemical properties of the cellular membrane...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28430359/sulfur-containing-gaseous-signal-molecules-ion-channels-and-cardiovascular-diseases
#18
REVIEW
Wen Yu, Hongfang Jin, Chaoshu Tang, Junbao Du, Zhiren Zhang
Sulfur-containing gaseous signal molecules including hydrogen sulfide (H2 S) and sulfur dioxide (SO2 ) were previously recognized as toxic gases. However, extensive studies have revealed that they can be generated in the cardiovascular system via a sulfur-containing amino acid metabolic pathway, playing an important part in cardiovascular physiology and pathophysiology. Ion channels are pore-forming membrane proteins present in the membrane of all biological cells; functions include establishing a resting membrane potential and controlling action potentials and other electrical signals by conducting ions across the cell membrane...
April 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28424587/interactions-of-the-mechanosensitive-channels-with-extracellular-matrix-integrins-and-cytoskeletal-network-in-osmosensation
#19
REVIEW
Runsheng Jiao, Dan Cui, Stephani C Wang, Dongyang Li, Yu-Feng Wang
Life is maintained in a sea water-like internal environment. The homeostasis of this environment is dependent on osmosensory system translation of hydromineral information into osmotic regulatory machinery at system, tissue and cell levels. In the osmosensation, hydromineral information can be converted into cellular reactions through osmoreceptors, which changes thirst and drinking, secretion of antidiuretic vasopressin (VP), reabsorption of water and salt in the kidneys at systemic level as well as cellular metabolic activity and survival status at tissue level...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28416581/trp-channels-in-brown-and-white-adipogenesis-from-human-progenitors-new-therapeutic-targets-and-the-caveats-associated-with-the-common-antibiotic-streptomycin
#20
Anna Goralczyk, Marc van Vijven, Mathilde Koch, Cedric Badowski, M Shabeer Yassin, Sue-Anne Toh, Asim Shabbir, Alfredo Franco-Obregón, Michael Raghunath
Transient receptor potential (TRP) channels are polymodal cell sensors responding to diverse stimuli and widely implicated in the developmental programs of numerous tissues. The evidence for an involvement of TRP family members in adipogenesis, however, is scant. We present the first comprehensive expression profile of all known 27 human TRP genes in mesenchymal progenitors cells during white or brown adipogenesis. Using positive trilineage differentiation as an exclusion criterion, TRP polycystic (P)3, and TPR melastatin (M)8 were found to be uniquely adipospecific...
April 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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